Interactions with exposed subendothelial extracellular proteins and cellular integrins (endothelial cells, platelets and lymphocytes) can cause alterations in the hemostatic system associated with atherothrombotic processes. Many molecules found in snake venoms induce pathophysiological changes in humans, cause edema, hemorrhage, and necrosis. Disintegrins are low molecular weight, non-enzymatic proteins found in snake venom that mediate changes by binding to integrins of platelets or other cells and prevent binding of the natural ligands such as fibrinogen, fibronectin or vitronectin. Disintegrins are of great biomedical importance due to their binding affinities resulting in the inhibition of platelet aggregation, adhesion of cancer cells, and induction of signal transduction pathways. RT-PCR was used to obtain a 216 bp disintegrin cDNA from a C. s. scutulatus snake venom gland. The cloned recombinant disintegrin called r-mojastin 1 codes for 71 amino acids, including 12 cysteines, and an RGD binding motif. r-Mojastin 1 inhibited platelet adhesion to fibronectin with an IC50 of 58.3 nM and ADP-induced platelet aggregation in whole blood with an IC50 of 46 nM. r-Mojastin 1 was also tested for its ability to inhibit platelet ATP release using PRP resulting with an IC50 of 95.6 nM. MALDI-TOF mass spectrum analysis showed that r-mojastin has a mass of 7.9509 kDa.

Elapid snakes throughout the world are considered very lethal containing neurotoxic venoms that affect the nervous system. When humans are envenomated it is considered a serious medical emergency, and antivenom is the main form of treatment considered, in spite of the fact that some patients may only survive under intensive therapy treatment such as respiratory support. Coral snakes are part of the family Elapidae and envenomations by these snakes are very low (< 2% of total snakebites) in most countries from southeastern United States to Argentina. In the United States there are only two species of coral snakes of medical importance which belong to the Micrurus genera: Micrurus fulvius fulvius (Eastern coral snake) and M. tener tener (Texas coral snake). In 2006, Wyeth pharmaceutical notified customers that the production of the North American Coral Snake Antivenin (NACSA) in the U.S. was discontinued and adequate supplies were available to meet historical needs through the end of October 2008; and therefore, it is of utmost important to consider other antivenoms as alternatives for the treatment of coral snake envenoming. One logical alternative is the coral snake antivenom, Coralmyn, produced by the Mexican company, Bioclon. In order to compare neutralization between NACSA and Coralmyn antivenoms with the North American coral snake venoms, the venom lethal doses (LD 50 ) and antivenom effective doses (ED 50 ) were determined in 18-20 g, female, BALB/c mice. Additionally, venom comparisons were determined through a non reduced SDS-PAGE for M. f. fulvius, M. t. tener and the Mexican coral snake venom, M. nigrocinctus nigrocinctus. Coralmyn antivenom was able to effectively neutralize 3 LD 50 doses of all venom from both M. t. tener and M. f. fulvius, while Wyeth antivenom only neutralized M. f. fulvius venom and was not effective in neutralizing 3 LD 50 doses of M. t. tener venom. Coralmyn is effective in the neutralization of both clinically important coral snake venoms in the U.S.

The haemostatic components of venom from the genus Porthidium has been poorly studied, although it is known that severe manifestations occur when humans are envenomed, which include invasive oedema and disseminated ecchymosis. The effects of venom on blood platelets are commonly studied and are normally carried out with platelet-rich plasma (PRP). A series of crude venom dilutions was used to determine the effects of adenosine diphosphate (2 microM) and adrenaline (11 microM) induced platelet aggregation. Venom of Porthidium lansbergii hutmanni was fractioned by anionic exchange chromatography, and the fractions were also used to determine the 50% inhibition of adenosine diphosphate (ADP) and adrenaline-induced platelet aggregating dose (AD50). Crude venom has more effect in inhibiting adrenaline-induced aggregation (AD50 = 0.0043 microg) followed by the adenosine diphosphate (AD50 = 17 microg). Peaks I and II obtained by chromatography also inhibited adrenaline-induced platelet aggregation with an AD50 of 3.2 and 0.013 microg, respectively, and both peaks inhibited ADP-induced platelet aggregation with an AD50 of 10 microg. The main purpose of this work was to characterise the in vitro effects caused by P. lansbergii hutmanni crude venom and its fractions on the platelet aggregation mediated by adrenaline and ADP agonists.

The Porthidium genus is represented by the P. lansbergii rozei and P. lansbergii hutmanni (Plh) subspecies in Venezuela. The venom components of these have been little studied, probably due to the low incidence of reported accidents, although acute and serious local effects such as invasive edema and disseminated ecchymosis are present during human envenonation. The aim of this work was to characterize the in vitro effects of crude P. l. hutmanni venom, and its fractions, on platelet aggregation triggered by two physiologic agonists: thrombin and collagen. The effects of thrombin and collagen were observed on a platelet-rich plasma (PRP) solution (3 x 10(5) platelets/microL) using serial dilutions of P. l. hutmanni venom (0.625-40 microg). The crude venom was fractionated by anionic exchange chromatography and two peaks obtained. Crude venom and both fractions were highly inhibitory on platelet aggregation mediated by the two agonists. The anti-aggregating dose (AD(50)) for both agonists was determined. PRP collagen-triggered aggregation was most inhibited by the crude venom (AD(50) = 0.67 microg) when compared with PRP thrombin-triggered aggregation (AD(50) = 4.92 microg). Collagen-induced aggregation was more intensely inhibited by venom than thrombin-induced aggregation. In conclusion, to specify the inhibition mechanisms involved for each of the active components in the venom from these subspecies, we must characterize and purify the inhibitors of aggregation from P. l. hutmanni venom, with the purpose of suggesting new pharmacological substances to be incorporated into the therapeutic arsenal to treat hemostatic pathologies related to high levels of platelet aggregation.